The medical use of ethylene-vinyl acetate copolymers is well known in the art [Biomaterials 2 201 (1981) J.Biomedical Materials Research 15 267 (1981)]. Controlled release pharmaceutical preparations for treating glaucoma, diabetes as well as controlled release contraceptives were prepared by using this copolymer. Because of its high biocompatibility [J. Biomedical Materials Research 15 267 (1981)] various human applications of this copolymer have been permitted by the FDA.
In view of the above, it is surprising that only a few oral applications are reported in the art and even these are developed for use as a mycoderma adhesive flexible films administered into the mouth cavity [Japanese Kokai Tokkyo Koka JP 6305, 756 8805,756, ibid, 61 93, 113 8693,113, ibid 6354, 318 885 4318] or in dentistry [European Patent Application EP 268464.]
No typical oral application, e.g. use as a base for tablets has been described.
In order to provide a preparation for oral administration we have selected morphine sulphate as an example for the active ingredient because retarding the release of this active substance is essential in analgesic treatment and, on the other hand, this medicament represents a whole family of salt-like active substances with excellent water solubility.
Various polymer systems are proposed for retarding the release of morphine sulphate. For example in J. Pharmacol. Methods 1(2) 21 (1978) and J. Pharm. Sci. 69(8) 980 (1980) dimethylsiloxane, in European Patent Application EP 205 282 a mycoderma adhesive cellulose composition, in French Patent Application Fr. 2,576 213 sulphate and carboxylate anion exchanger, in Rev. Asoc. Esp. Farm. Hosp. 11(1) 111 (1987) PVC and Methacel K-15 M, in ACS. Symp. Ser. 348 (1987) polyethylene oxide and in Br.J. Anaesth 61 221 (1988) crosslinked ethylene oxide are described. According to the above prior art references these polymer systems are suitable for retarding the release of the morphine sulphate but do not ensure simultaneously the wide variability of the dissolution profile and the dissolution rate.